TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16215	48868;48869;48870	chr2:178614964;178614963;178614962	chr2:179479691;179479690;179479689
N2AB	14574	43945;43946;43947	chr2:178614964;178614963;178614962	chr2:179479691;179479690;179479689
N2A	13647	41164;41165;41166	chr2:178614964;178614963;178614962	chr2:179479691;179479690;179479689
N2B	7150	21673;21674;21675	chr2:178614964;178614963;178614962	chr2:179479691;179479690;179479689
Novex-1	7275	22048;22049;22050	chr2:178614964;178614963;178614962	chr2:179479691;179479690;179479689
Novex-2	7342	22249;22250;22251	chr2:178614964;178614963;178614962	chr2:179479691;179479690;179479689
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-5
• Domain position: 61
• Structural Position: 92
• Q(SASA): 0.4093
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
E/K	None	None	0.103	N	0.261	0.222	0.156986980423	gnomAD-4.0.0	6.91755E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.06434E-07	0	0
E/Q	rs1193666714	None	0.103	N	0.389	0.115	0.117506650769	gnomAD-4.0.0	6.91755E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.06434E-07	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
E/A	0.146	likely_benign	0.1797	benign	-0.845	Destabilizing	0.896	D	0.637	neutral	N	0.476966955	None	None	N
E/C	0.8099	likely_pathogenic	0.8709	pathogenic	-0.326	Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
E/D	0.3823	ambiguous	0.4464	ambiguous	-0.708	Destabilizing	0.896	D	0.525	neutral	N	0.478471322	None	None	N
E/F	0.8259	likely_pathogenic	0.8759	pathogenic	-0.29	Destabilizing	0.996	D	0.775	deleterious	None	None	None	None	N
E/G	0.3877	ambiguous	0.4593	ambiguous	-1.161	Destabilizing	0.896	D	0.671	neutral	N	0.475053061	None	None	N
E/H	0.5571	ambiguous	0.653	pathogenic	-0.338	Destabilizing	0.988	D	0.592	neutral	None	None	None	None	N
E/I	0.2899	likely_benign	0.3707	ambiguous	0.004	Stabilizing	0.988	D	0.771	deleterious	None	None	None	None	N
E/K	0.1821	likely_benign	0.2415	benign	-0.134	Destabilizing	0.103	N	0.261	neutral	N	0.407050758	None	None	N
E/L	0.3354	likely_benign	0.4291	ambiguous	0.004	Stabilizing	0.919	D	0.675	prob.neutral	None	None	None	None	N
E/M	0.3568	ambiguous	0.4416	ambiguous	0.348	Stabilizing	0.997	D	0.771	deleterious	None	None	None	None	N
E/N	0.3991	ambiguous	0.5017	ambiguous	-0.705	Destabilizing	0.919	D	0.537	neutral	None	None	None	None	N
E/P	0.5307	ambiguous	0.5874	pathogenic	-0.258	Destabilizing	0.988	D	0.693	prob.neutral	None	None	None	None	N
E/Q	0.1345	likely_benign	0.173	benign	-0.595	Destabilizing	0.103	N	0.389	neutral	N	0.452642185	None	None	N
E/R	0.295	likely_benign	0.3741	ambiguous	0.152	Stabilizing	0.851	D	0.517	neutral	None	None	None	None	N
E/S	0.3119	likely_benign	0.3982	ambiguous	-0.942	Destabilizing	0.919	D	0.53	neutral	None	None	None	None	N
E/T	0.2011	likely_benign	0.2489	benign	-0.669	Destabilizing	0.919	D	0.645	neutral	None	None	None	None	N
E/V	0.1508	likely_benign	0.19	benign	-0.258	Destabilizing	0.968	D	0.691	prob.neutral	N	0.427564643	None	None	N
E/W	0.9443	likely_pathogenic	0.9619	pathogenic	0.035	Stabilizing	0.999	D	0.769	deleterious	None	None	None	None	N
E/Y	0.7541	likely_pathogenic	0.8181	pathogenic	-0.008	Destabilizing	0.996	D	0.776	deleterious	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.